ABSTRACT
This chapter describes the principles and process design considerations for freezing and thawing protein solutions on a large scale. Freeze-thaw systems designed to handle bulk product volumes greater than 100 L have been used for several years at Genentech, Inc., as a method for preserving formulated and preformulated bulk parenteral biopharmaceutical products. The chapter describes use of a portable, jacketed, stainless steel vessel with internal heat transfer surfaces. Its design is consistent with conventional pharmaceutical manufacturing and current good manufacturing practices. Important considerations for the large-scale freezing process includes minimizing freezing time, minimizing convection, promoting dendritic ice growth, minimizing cryoconcentration, avoiding mechanical stresses in the vessel, and providing a sanitary vessel design. Important considerations for the large-scale thawing process include avoiding overheating the product by maintaining tight control of the vessel wall temperature and maximizing convection in the liquid phase.
